Faridoxorubicin

LONDON and PHILADELPHIA, Jan. 20, 2026 (GLOBE NEWSWIRE) -- Avacta Therapeutics (AIM: AVCT), a clinical stage biopharmaceutical company developing pre|CISION ® , a tumor-activated oncology delivery platform, has published a trading update for the year ended December 31, 2025. The Company made excellent progress during 2025, developing its unique industry-leading technology platform, pre|CISION ® , with two programs anticipated to be in clinical development in 2026. The Company raised £22.5m in equity during 2025 to support the investment in its programs. Highlights Research and Development Faridoxorubicin (AVA6000) program In December 2025 Avacta reported highly encouraging efficacy and safety data from the cohort of patients enrolled with salivary gland cancer where a disease control rate of 90% is maintained in the full cohort ( link ) Program continued to enroll patients in the Phase 1b expansion cohorts, to assess the efficacy of faridoxorubicin in more homogenous, defined patient populations to better predict the magnitude of efficacy anticipated in larger Phase 2/3 trials. FAP-Exd (AVA6103) program In December 2025 Avacta reported new pharmacology data in support of the IND process and the design of the Phase 1 trial was published in parallel ( link ) Clinical testing expected to initiate in Q1 2026, subject to clearance by regulators. Multiple U.S. specialty oncology centers are expected to open with key investigators of different specialties to enroll the four selected tumor types: pancreatic cancer, gastric cancer, small cell lung cancer and cervical cancer. Intellectual property (IP) portfolio continued to grow and gain momentum measured by increased IP filings. These include two important advances in the pre|CISION ® IP estate: the sustained release mechanism of payload delivery, piloted in the AVA6103 program, which is anticipated to begin clinical testing in Q1 2026; and the dual payload mechanism of delivery allowing the precise delivery of two payloads to the tumor with all of the benefits of the pre|CISION ® technology. Financial The Company successfully raised £22.5m in new equity during 2025 from a broad range of existing and new investors to support R&D programs and also renegotiated the terms of the convertible bond ( link ) Unaudited cash and cash equivalents as of December 31, 2025: £16.9m providing a runway into Q3 2026 supporting the planned spend on the Group’s two clinical stage programs and preclinical pipeline to key value inflection points. Outlook for 2026 Faridoxorubicin (AVA6000) program. Multiple data updates in both patient groups, with salivary gland cancers and with triple negative breast cancer updates expected in H1 2026. Beginning of the FAP-Exd (AVA6103) clinical testing expected in Q1 2026. A group of U.S. clinical trial specialty centers are expected to open imminently with key investigators of different specialties to enroll the four selected tumor types: pancreatic cancer, gastric cancer, small cell lung cancer and cervical cancer. Preliminary data from this trial is anticipated in the second half of 2026. Continued active interaction with potential partners regarding both faridoxorubicin (AVA6000) and FAP-Exd (AVA6103). The survival data in the SGC indication continues to mature, allowing planning of the next stage of development with potential partners ( link ). The initiation of the FAP-Exd clinical trial continues to be of interest in the market. Christina Coughlin MD, PhD, CEO of Avacta, commented : "We gained real traction with our R&D programs, based on our unique industry leading technology, pre|CISION ® , during 2025. There are no other technologies that can deliver cancer treatment drugs directly into the tumor at the concentrations that our payloads enable without causing highly toxic side effects. “Our sustained release mechanism piloted in the FAP-Exd (AVA6103) program is anticipated to begin clinical testing this quarter, a significant milestone achievement, just 24 months after the beginning of the program. This program continues to garner significant interest from global pharmaceutical companies; however, the Company’s strategy remains to retain 100% of AVA6103 until we begin to see readouts from the Phase 1a clinical trial. Importantly, the trial has been designed to rapidly deliver clinical data in this program. “We are developing further IP around the pre|CISION ® platform. Drug development isn’t just about science, it is about strategy and protecting our innovation. Our IP estate is the most valuable asset we have. To further this IP estate, we also raised over £22m to support our research and development programs, which gives us a runway into Q3 2026. These funds allow the Company to initiate the AVA6103 clinical trial and we anticipate the initial data in the AVA6103 program in the second half of 2026. “The unique nature of the dual payload program is also generating interest and we are exploring opportunities with multiple potential partners with a view to investigating the wide utility of this novel technology. “We continue to have multiple conversations with global pharmaceutical companies regarding our full pipeline. We are incredibly excited for the year ahead, which the board believes will be a transformative period for the Company, patients and our shareholders.” Operational update Faridoxorubicin (AVA6000) Highly encouraging data were presented last month describing the efficacy observed in the patients treated in the Phase 1b expansion cohort, which appears highly similar to the data observed in the Phase 1a patient population ( link ). The larger numbers of patients treated in this cohort are important to inform the design and size of a subsequent trial in this indication. Importantly, the prolonged PFS observed in the Phase 1a cohort of patients indicates a prolonged PFS in the Phase 1b cohort. Although these data can take time to collect, the Company is encouraged by the extended survival observations in the trial. Attention to this stage of development is designed to derisk later stages of clinical trials. The data in the Phase 1a portion of the trial were updated at ESMO ( link ), where the PFS was reported as highly encouraging when compared with benchmark data in this indication. As the data in the Phase 1b expansion cohort are preliminary, the Company continues to collect the data. The estimates of the PFS and overall survival (OS) will be used to design the randomized study in this indication. In addition, the Company expects to release data in the TNBC cohort in H1 2026. Further development of faridoxorubicin will be undertaken subject to a partner being secured. The Company continues to engage with multiple partners as the data matures. FAP-Exd (AVA6103) Recent pharmacology data ( link ) have been released demonstrating several key aspects of the FAP-Exd (AVA6103) program, including: Robust efficacy in a broad range of patient-derived cancer models with deep complete responses observed with only three doses of FAP-Exd, even in settings of low FAP expression. In an encouraging parallel, the durability of the responses in the preclinical setting with FAP-Exd match those observed among patients with salivary gland cancers, treated with faridoxorubicin even in the setting of low FAP expression ( link ). Tumor and plasma exposure studies have demonstrated that FAP-Exd rapidly penetrates the tumor microenvironment (TME), is held intact for over five days in the tumor and releases exatecan, with an observed high maximal concentration (C max ) in the tumor within minutes and very low exposure in the bloodstream which is undetectable within two hours. The FAP-Exd Phase 1 trial design has been released ( link ) and includes the following aspects to optimize the execution of this study: The trial will enroll patients with a selected set of four cancer indications predicted by AI (in our strategic collaboration with Tempus AI) to be the most sensitive among solid tumor indications. These include pancreatic cancer, small cell lung cancer, gastric cancer and cervical cancer. Importantly, each of these four disease settings has a favorable regulatory path forward and the group includes both large tumor types as well as potential orphan indications. Clinical trial sites in the U.S. and the trial investigators have been selected based on their deep experience with these indications. The Company has enjoyed strong interest among clinical trial sites and investigators in the study. The trial design has two key features to optimize the rapid collection of data: Two independent arms investigating two schedules with every two weeks dosing (Q2W) and every three weeks dosing (Q3W) are anticipated to enroll in parallel, and; The trial will use the Bayesian Optimal Interval (BOIN) design, a modern statistical method for oncology Phase 1 trials. BOIN combines the simplicity of the traditional 3+3 enrollment method, where small groups of patients are treated at increasing doses, with efficient dose exploration and flexible enrollment into cohorts to optimize data collection over the course of the trial. This approach has been shown to enable the trial to handle complex findings and rapidly identify the optimal dose range. Dual Payload Technology (AVA6207) The work in the AVA6103 program to better define the self-immolative linker technology led to the invention of the dual payload technology ( link ). The dual payload platform is enabled by the insertion of two payload attachment points in the linker, ensuring the independent release of both payloads with a single FAP cleavage event. The release of two payloads in one pre|CISION ® medicine has three key advantages: Combination therapy is the mainstay of how patients are treated in oncology. The challenge is the toxicities with each individual drug. With a single pre|CISION ® medicine, a simple monotherapy trial is needed and both payloads have the benefits of the pre|CISION ® technology: concentration in the TME and minimal exposure in normal tissues. The release of dual payloads is accomplished without the need for a biologic arm (e.g. an antibody, Fc region or Affimer) which greatly simplifies the manufacturing of these medicines. Indeed, all pre|CISION ® medicines are small molecules, meaning short and chemical-based manufacturing that is more cost-efficient than biologics. Because the size of the molecule is small, rapid and efficient tumor penetration of two payloads is anticipated based on the data presented with FAP-Exd, where tumor cells will see both payloads in parallel. The design of the first program combines a topoisomerase I inhibitor with a second payload that can overcome a key resistance mechanism, namely the DNA Damage Repair pathway (DDR). Preclinical data presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (October, 2025) demonstrates preliminary synergy of this combination ( link ). The Company has committed to the selection of the payloads for the AVA6207 program in 2026. Financial update The Company raised £22.5m in equity (gross) to support its investment programs during the year and also realized just over £15m from the disposal of the non-core diagnostics businesses. The Company renegotiated the terms of the convertible bond with the Quarterly Convertible Bond repayments and interest in January 2026 and April 2026 payment dates deferred until October 2027. In addition, the bondholder has the right to accelerate the satisfaction of the deferred repayments based on agreed conditions and the conversion price of the convertible bond is reset at 75.0p. All conditions of the bond renegotiation are reported here ( link ). Unaudited cash and cash equivalents at as December 31, 2025, were £16.9m, providing the Company with a runway into Q3 2026 to support its research and development activities. For further information from Avacta, please contact: Avacta Group plc Christina Coughlin, Chief Executive Officer via ICR Healthcare Strand Hanson Limited (Nominated Adviser) James Harris / Chris Raggett / James Dance Zeus (Broker) James Hornigold / George Duxberry / Dominic King ICR Healthcare Mary-Jane Elliott / Jessica Hodgson / Stephanie Cuthbert avacta@consilium-comms.com Investor Contact Renee Leck THRUST Strategic Communications renee@thrustsc.com Media Contact Carly Scaduto THRUST Strategic Communications carly@thrustsc.com About Avacta - Avacta Therapeutics is a clinical-stage life sciences company expanding the reach of highly potent cancer therapies with the pre|CISION ® platform. pre|CISION ® is a proprietary payload delivery system based on a tumor-specific protease (fibroblast activation protein or FAP) that is designed to concentrate highly potent payloads in the tumor microenvironment while sparing normal tissues. Our innovative pipeline consists of pre|CISION ® peptide drug conjugates (PDC) or Affimer ® drug conjugates (AffDC) that leverage the tumor-specific release mechanism, providing unique benefits over traditional antibody drug conjugates. The pre|CISION ® platform comprises an anticancer payload conjugated to a proprietary peptide that is a highly specific substrate for fibroblast activation protein (FAP) which is upregulated in most solid tumors compared with healthy tissues. The pre|CISION ® platform harnesses this tumor specific protease to cleave pre|CISION ® peptide drug conjugates and pre|CISION ® antibody/Affimer ® drug conjugates in the tumor microenvironment, thus releasing active payload in the tumor and reducing systemic exposure and toxicity, allowing dosing to be optimized to deliver the best outcomes for patients.

2025年12月17日消息——Avacta Therapeutics （AIM: AVCT）是一家临床阶段的生物制药公司，开发pre - |CISION®，一种肿瘤激活的肿瘤递送平台，今天宣布了正在进行的法多柔比星（AVA6000） 1b期试验的唾液腺癌（SGC）患者的令人信服的新数据。 https://avacta.com/faridoxorubicin-ava6000-phase-1b-cohort-demonstrates-clinically-meaningful-tumor-shrinkage-in-patients-with-salivary-gland-cancers/ Faridoxorubicin（也称AVA6000或FAP-Dox）是英国生物制药公司Avacta Therapeutics开发的创新肿瘤治疗药物，属于其pre|CISION®平台的领头产品。它是一种多柔比星（doxorubicin）的肽药物偶联物（peptide drug conjugate），旨在解决传统蒽环类药物的心脏毒性等系统性副作用问题。目前处于I期临床阶段，最新数据（截至2025年12月）显示出良好的安全性和初步疗效，尤其在唾液腺癌（salivary gland cancer, SGC）和软组织肉瘤等领域表现出色。 Faridoxorubicin 1. 靶点：成纤维细胞激活蛋白（FAP） Faridoxorubicin的靶点是成纤维细胞激活蛋白（Fibroblast Activation Protein, FAP）。FAP是一种在大多数上皮源性实体瘤的肿瘤相关成纤维细胞（CAFs）中高表达的蛋白酶，而在正常成人组织中表达极低或无表达。这使得FAP成为理想的肿瘤微环境（TME）靶点，用于实现药物在肿瘤部位的选择性激活。 2. 作用机制（MOA） Faridoxorubicin是一种前药形式的多柔比星，通过肽链偶联，使其在全身循环中保持无活性状态。只有当药物到达肿瘤微环境，被高表达的FAP蛋白酶切割后，多柔比星才被释放出来，直接在肿瘤部位发挥细胞毒作用。 - 核心优势：显著降低系统性暴露，减少传统多柔比星常见的心脏毒性、骨髓抑制等副作用。 - 与传统多柔比星相比，可实现更高剂量给药（临床中最高达385 mg/m²，相当于传统多柔比星的4倍），从而提升抗瘤效能。 - 多柔比星释放后，通过DNA嵌入、拓扑异构酶II抑制和自由基产生等经典机制诱导肿瘤细胞凋亡。 这一机制验证了pre|CISION®平台的潜力：通过肿瘤微环境特异性酶激活，实现“靶向释放”。 3. 临床结果解读（含与传统多柔比星对比） Faridoxorubicin目前处于I期剂量爬坡（Phase 1a）和扩展（Phase 1b）阶段，主要针对FAP阳性实体瘤患者。最新数据（2025年12月17日更新）显示： - 安全性：在唾液腺癌（SGC）队列中，未观察到严重心脏毒性事件，即使累积暴露相当于传统多柔比星550 mg/m²（传统剂量上限通常为450 mg/m²以避免心脏风险）。整体毒性显著低于传统多柔比星。 - 疗效（重点在唾液腺癌SGC队列）：   - 合并Phase 1a和1b数据，在≥250 mg/m²剂量组的30例SGC患者中：疾病控制率（DCR）约90%，9例患者观察到临床意义肿瘤缩小，包括2例确认部分缓解（PR，>30%缩小）和7例微小缓解（MR，10-30%缩小）。   - 中位无进展生存期（mPFS）尚未达到，中位随访超过15周（Phase 1b），整体提示耐久响应。相比历史基准数据（EORTC等研究，传统化疗mPFS 3.5-6个月），可能翻倍以上。 与传统多柔比星临床结果对比： - 在唾液腺癌（SGC）：   - 传统多柔比星（单药或含多柔比星方案如CAP）：客观缓解率（ORR）通常<20-35%，DCR较低，mPFS约4-7个月（历史研究，如CAP方案ORR 18-46%，但毒性高；单药多柔比星活性有限）。   - Faridoxorubicin：更高DCR（90-91%）、更多肿瘤缩小（包括PR和MR）、潜在更长PFS，且安全性显著改善（无严重心脏毒性，高剂量耐受）。 - 在软组织肉瘤（STS）：   - 传统多柔比星单药（75 mg/m²）：ORR 12-20%，mPFS 4.6-6.8个月。   - Faridoxorubicin：早期信号显示肿瘤响应，即使在低剂量组；允许更高累积剂量，潜在提升疗效而降低心脏风险。 这些结果表明，Faridoxorubicin在难治性SGC（无标准治疗方案）中具有突破潜力，并为平台验证提供了强有力证据。Phase 1b数据仍在更新，预计2026年有更多读出。 4. 国内外临床情况 国外临床情况：Faridoxorubicin的临床试验主要在欧美开展。Phase 1试验（ALS-6000-101）为多中心研究，试验地点包括英国多家医院（如皇家马斯登医院等）和美国知名癌症中心（如Memorial Sloan Kettering Cancer Center纽约、Fred Hutchinson Cancer Center西雅图等）。截至2025年12月，Phase 1a剂量爬坡已完成，Phase 1b扩展队列正在招募中，重点评估唾液腺癌等适应症的安全性和初步疗效。公司计划基于这些数据推进至II期注册研究。 国内临床情况：目前Faridoxorubicin尚未在中国开展临床试验，也无公开的中国或亚洲试验计划公告。作为一款处于早期临床阶段的英国公司药物，未来若推进全球多区域试验，可能考虑引入中国，但现阶段无相关进展。 5. 市场前景 唾液腺癌（SGC）是一种罕见、预后差的头颈部肿瘤，年发病率低（全球约数万例），但缺乏有效标准治疗，现有化疗（如多柔比星单药）疗效有限且毒性高。Faridoxorubicin在SGC中的高DCR和潜在PFS改善，显示出成为该适应症新标准治疗的潜力，可能获孤儿药地位和加速审批。 更广义上，pre|CISION®平台适用于多种FAP高表达实体瘤（如乳腺癌、胰腺癌、软组织肉瘤），多柔比星作为广谱化疗药，改进版有望重振蒽环类在晚期肿瘤中的地位。公司计划2026年进入II期（SGC和TNBC），若数据持续积极，授权合作或独立推进均有可能。 市场潜力：罕见瘤起步，扩展至大适应症，平台价值可达数十亿级别（类似ADC平台）。 6. 竞争格局 - 直接竞争：传统多柔比星及脂质体多柔比星（Doxil）仍是蒽环类主力，但心脏毒性限制累积剂量。Faridoxorubicin通过靶向释放显著改善安全性，无直接同类。 - 类似技术：ADC领域（如Enhertu、Trodelvy）火热，但Faridoxorubicin作为PDC（肽药物偶联），分子量更小、渗透更好、无抗体相关毒性。其他FAP靶向药物（如FAP-ILDra等放射偶联物）处于早期阶段，未有成熟竞争者。 - 优势定位：在毒性敏感患者（如心脏基础病）或需高剂量化疗的瘤种中，具有差异化竞争力。潜在挑战：需进一步II/III期验证疗效优越性。 总体而言，Faridoxorubicin代表了化疗药物“精准化”趋势，若后续数据确认，将在肿瘤治疗中占据重要位置。 Faridoxorubicin的进展令人期待，pre|CISION®平台或将开启肿瘤靶向化疗新时代。关注后续临床更新！（数据截至2025年12月21日） Avacta 正在利用 pre|CISION® 平台开发一系列资产： 后续项目：平台还正在开发其他有效载荷的前药，如喜树碱类等。 关注我们，下期聊更多前沿。健康，从觉醒开始！点赞、转发吧~